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Loncastuximab (Monograph)

Brand name: Zynlonta
Drug class: Antineoplastic Agents
- Antibody-drug Conjugates
- ADCs
Chemical name: Immunoglobulin G1, (anti-human CD19 (antigen)) (humanized clone RB4v1.2 κ1-chain), disulfide with humanized clone RB4v1.2 κ-chain, dimer, bis(thioether) with N-[31-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1,29-dioxo4,7,10,13,16,19,22,25-octaoxa-28-azahentriacont-1-yl]-L-valyl-N-[4- [[[[(11S,11aS)-8-[[5-[[(11aS)-5,11a-dihydro-7-methoxy-2-methyl-5-oxo-1Hpyrrolo[2,1-c][1,4]benzodiazepin-8-yl]oxy]pentyl]oxy]-11,11a-dihydro-11- hydroxy-7-methoxy-2-methyl-5-oxo-1H-pyrrolo[2,1-c][1,4]benzodiazepin10(5H)-yl]carbonyl]oxy]methyl]phenyl]-L-alaninamide
Molecular formula: C6544H10048N1718O2064S52
CAS number: 1879918-31-6

Medically reviewed by Drugs.com on Dec 4, 2023. Written by ASHP.

Introduction

Antineoplastic agent; a CD19-directed antibody-drug conjugate consisting of a humanized monoclonal IgG1 kappa antibody linked to an alkylating agent (SG3199).

Uses for Loncastuximab

B-cell Lymphoma

Treatment of relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma, previously treated with ≥2 systemic therapies (designated an orphan drug by FDA for this use).

Efficacy based on overall response rate; clinical benefit (e.g., improvement in survival, amelioration of disease-related symptoms) not established.

Loncastuximab Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Premedication and Prophylaxis

Dispensing and Administration Precautions

Administration

IV Administration

Administer via IV infusion. Loncastuximab tesirine lyophilized powder for injection must be reconstituted and diluted prior to administration.

Compatible with infusion bags containing polyvinylchloride (PVC), polyolefin (PO), and PAB (copolymer of ethylene and propylene). Administer final diluted solution through a 0.2 or 0.22-µm inline or add-on filter and catheter.

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.

Reconstitution

Reconstitute vial containing 10 mg of loncastuximab tesirine with 2.2 mL of sterile water for injection to provide a solution containing 5 mg/mL; direct diluent toward the wall of the vial. Gently swirl vial to ensure dissolution. Do not shake reconstituted solution.

Reconstituted solution should be clear to slightly opalescent, colorless to slightly yellow in color, and free of visible particulates. Use within 4 hours of reconstitution.

Protect from direct sunlight until time of use; do not freeze.

Discard partially used vials.

Dilution

Dilute appropriate dose in 50 mL of 5% dextrose. Mix the diluted solution by gentle inversion.

Use diluted solution immediately or store at 2–8°C for up to 24 hours or at 20–25°C for up to 8 hours.

Rate of Administration

Administer by IV infusion over 30 minutes.

Dosage

Adults

Body mass index <35 kg/m2: Calculate dosage based on actual body weight.

Body mass index ≥35 kg/m2: Calculate dosage based on adjusted body weight using the following formula:

Adjusted body weight (in kg) = 35 kg/m2 × (height in meters)2.

B-cell Lymphoma
IV

Cycles 1 and 2: 0.15 mg/kg once on day 1 of each 21-day cycle

Subsequent cycles: 0.075 mg/kg on day 1 of each 21-day cycle.

Dosage Modification for Toxicity

Some adverse effects require temporary interruption and/or dosage reduction or discontinuance of therapy.

If toxicity delays administration by >3 weeks, reduce subsequent doses of loncastuximab tesirine by 50%. However, if dosage reduction is necessary after cycles 1 and 2 of loncastuximab tesirine 0.15 mg/kg, the patient should receive 0.075 mg/kg for cycle 3 onward.

Consider discontinuing therapy if toxicity recurs after dosage reduction.

Hematologic Toxicity

If ANC is <1000/mm3 or platelet count is <50,000/mm3, withhold loncastuximab tesirine until recovery of ANC ≥1000/mm3 or platelet count ≥50,000/mm3.

Edema or Effusion

If edema or effusion of grade 2 or higher occurs, withhold loncastuximab tesirine therapy until toxicity resolves to grade 1 or lower.

Other Adverse Reactions

If grade 3 or higher nonhematologic adverse reactions occur, withhold loncastuximab tesirine until toxicity resolves to grade 1 or lower, then resume therapy.

Special Populations

Dosage in Hepatic Impairment

Mild hepatic impairment (bilirubin concentration not exceeding ULN with AST concentration exceeding the ULN, or bilirubin concentration <1–1.5 times ULN with any AST concentration): No dosage adjustment required.

Moderate or severe hepatic impairment (bilirubin concentration >1.5 times ULN with any AST concentration): No recommended dose established.

Dosage in Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Loncastuximab

Contraindications

Warnings/Precautions

Effusion and Edema

Grade 3 edema (most commonly ascites or peripheral edema) and pleural effusion reported.

Initiate medical management if grade 2 or higher edema or effusion occur; withhold loncastuximab tesirine until resolved.

Diagnostic imaging may be necessary in patients experiencing symptoms of pleural or pericardial effusion.

Myelosuppression

Grade 3 or 4 anemia, neutropenia, and thrombocytopenia.

Monitor CBC during treatment with loncastuximab tesirine and consider prophylactic G-CSF as appropriate. May need to interrupt therapy, reduce dose, and/or permanently discontinue loncastuximab tesirine depending on severity and persistence of myelosuppression.

Infectious Complications

Serious infections reported in 10% of patients receiving loncastuximab tesirine-lpyl in clinical trials; 2% of serious infections have been fatal. Pneumonia and sepsis were the most frequently reported infections.

Monitor for signs and symptoms of infection during treatment with loncastuximab tesirine. If grade 3 or 4 infection occurs, withhold loncastuximab tesirine until infection resolves, then resume therapy.

Cutaneous Reactions

Severe cutaneous reactions, including erythema, photosensitivity, and rash (including maculopapular and exfoliative rash) reported.

Monitor for new or worsening cutaneous reactions, including photosensitivity reactions, during treatment with loncastuximab tesirine. If cutaneous reactions or rash develop, consider dermatologic consultation.

Advise patients to minimize or avoid direct natural or artificial sunlight (including exposure through glass windows); patients should wear sun-protective clothing or use sunscreen. May need to interrupt therapy, reduce dose, and/or permanently discontinue loncastuximab tesirine depending on severity and persistence of severe cutaneous reaction.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.

SG3199 may cause embryotoxic and fetotoxic effects.

Advise pregnant females of the potential risk to the fetus. Advise females of reproductive potential and males who are partners of such females to use an effective method of contraception while receiving the drug and for 9 or 6 months, respectively, after the last dose.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Unknown whether loncastuximab is distributed into milk in humans.

Discontinue breast-feeding during therapy and for 3 months following the last dose.

Females and Males of Reproductive Potential

Verify pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential and males who are partners with such females to use an effective method of contraception during therapy and for 9 or 6 months, respectively, after the last dose.

May impair male fertility.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.

Hepatic Impairment

Pharmacokinetics of loncastuximab tesirine is not affected by mild hepatic impairment (bilirubin concentration not exceeding ULN with AST concentration exceeding ULN, or bilirubin concentration <1–1.5 times ULN with any AST concentration); however, exposure to unconjugated SG3199 may be increased.

Data are not available for patients with moderate (bilirubin concentration >1.5-3 times ULN with any AST concentration) or severe (bilirubin >3 times ULN with any AST concentration) hepatic impairment.

Renal Impairment

Pharmacokinetics not affected by mild or moderate renal impairment (Clcr ≥30 mL/min).

Not studied in patients with severe renal impairment (Clcr <30 mL/min) or in patients with end-stage renal disease, including those undergoing dialysis.

Common Adverse Effects

Adverse effects occurring in ≥20% of patients receiving loncastuximab tesirine include thrombocytopenia , increased gamma-glutamyltransferase , neutropenia, anemia , hyperglycemia , elevated concentrations of aminotransferase , fatigue , hypoalbuminemia , rash , edema , nausea , and musculoskeletal pain.

Drug Interactions

SG3199 (small molecule cytotoxic component of loncastuximab tesirine) is metabolized by CYP3A4 and 3A5.

SG3199: Substrate of P-glycoprotein. Not a substrate of breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, or organic cation transporter (OCT) 1. Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5, P-gp, BCRP, OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, OCT2, OCT1, multi-antimicrobial extrusion protein (MATE) 1, MATE2-K, or bile salt export pump (BSEP).

Loncastuximab Pharmacokinetics

Absorption

Bioavailability

Exposure to loncastuximab tesirine and the anti-CD19 antibody increase with increasing dose.

Distribution

Extent

Not known whether loncastuximab tesirine is distributed into human milk.

Elimination

Metabolism

SG3199 is metabolized by CYP3A4 and 3A5.

Elimination Route

Not expected to undergo substantial renal excretion.

Half-life

Mean half-life: 20.8 days.

Special Populations

No differences in pharmacokinetics observed based on age, sex, race, body weight or Eastern Cooperative Oncology Group (ECOG) status (0 or 2), or mild to moderate renal impairment.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package to protect from light. Do not freeze.

Compatibility

Parenteral

Solution Compatibility

Compatible

Dextrose 5% in water

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Loncastuximab tesirine-lpyl

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion only

10 mg

Zynlonta

ADC Therapeutics America Inc.

AHFS DI Essentials™. © Copyright 2024, Selected Revisions December 13, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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